TGIF1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- TGIF1 (HGNC:11776) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- TGFB induced factor homeobox 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- HPE4, TGIF
- Alias symbols
- No aliases found
- %HI
- 30.39(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.01(Read more about gnomAD pLI score)
- LOEUF
- 0.91(Read more about gnomAD LOEUF score)
- Cytoband
- 18p11.31
- Genomic Coordinates
-
GRCh37/hg19: chr18:3412007-3459976 NCBI Ensembl UCSC GRCh38/hg38: chr18:3412009-3459978 NCBI Ensembl UCSC - MANE Select Transcript
- NM_003244.4 ENST00000343820.10 (Read more about MANE Select)
- Function
- Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adu... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-13645
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
05/10/2012
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- holoprosencephaly 4 Monarch
HI Evidence:
-
PUBMED:
16962354
El-Jaick et al. (2007) sequenced TGIF1 in 435 individuals with HPE and detected 4 mutations in TGIF1, including a de novo nonsense mutation. The authors also recapitulate the functional studies by Gripp et al. (2000).
-
PUBMED:
12522553
Aguilella et al. (2003) sequenced TGIF1 in 127 HPE individuals and found 2 mutations, including 1 nonsense mutation. The nonsense mutation was inherited from a father with hypotelorism and cleft lip, microsigns of HPE, but no ID.
-
PUBMED:
22125506
Keaton et al. report seven individuals with mutations or deletions (large or focal) involving TGIF1 and also summarize data from other publications. Two frameshift LOF mutations (p.Phe86Serfs*13, p.Arg260Glyfs*58) and one "focal gene deletion" found in this study alone.
HI Evidence Comments:
PMID:10835638: Gripp et al. (2000) sequenced TGIF1 in 268 individuals with HPE and found 4 heterozygous missense mutations. One of these mutations (S28C) was also seen in the father and grandfather of the proband, both of whom had ocular hypotelorism, a microsign of HPE, suggesting this mutation segregates with the phenotype. A de novo P36R mutation was described and functional studies of the mutant protein indicated decreased binding to the TGIF1 target site and loss of transcriptional regulatory activity in multiple assays. The other mutations were not as well characterized.
PMID:
Mutations in TGIF1 display incomplete penetrance and variable expressivity.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No Identified Literature.
Genomic View
Select assembly:
(NC_000018.9)
(NC_000018.10)